The Role of α-Synuclein in Neurodegenerative Diseases: From Molecular Pathways in Disease to Therapeutic Approaches

Author(s): Karima M. Al-Mansoori , Mohamed Y. Hasan , Abdulmonem Al-Hayani , Omar M.A. El-Agnaf .

Journal Name: Current Alzheimer Research

Volume 10 , Issue 6 , 2013

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Abstract:

Parkinson disease (PD) is the second most prevalent neurodegenerative disorder after Alzheimer’s disease (AD). The formation of the cytoplasmic inclusions named “Lewy bodies” in the brain, considered to be a marker for neuronal degeneration in PD and dementia with Lewy bodies. However, Lewy bodies (LBs) are also observed in approximately 60 percent of both sporadic and familial cases with AD. LBs consist of fibrils mainly formed by post-translational modified α-synuclein (α-syn) protein. The modifications can be truncation, phosphorylation, nitration and mono-, di-, or tri-ubiquitination. Development of disease seems to be linked to events that increase the concentration of α-syn or cause its chemical modification, either of which can accelerate α-syn aggregation. Examples of such events include increased copy number of genes, decreased rate of degradation via the proteasome or other proteases, or modified forms of α-syn. As the aggregation of α-syn in the brain has been strongly implicated as a critical step in the development of several neurodegenerative diseases, the current search for disease-modifying drugs is focused on modification of the process of α-syn deposition in the brain. Recently researchers have screened and designed various molecules that are selectively focused on inhibiting or preventing α-syn aggregation and toxicity. Another strategy that has emerged is to target α-syn expression as a potential therapy for neurodegenerative diseases associated with LBs.

Keywords: Alpha-synuclein, alzheimer’ s disease, drug discovery, lewy bodies, neurodegeneration, parkinson’ s disease, dementia with lewy bodies and protein aggregation.

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Article Details

VOLUME: 10
ISSUE: 6
Year: 2013
Page: [559 - 568]
Pages: 10
DOI: 10.2174/1567205011310060002
Price: $58

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